Laser wave mixing has been described in many patents, journals and articles. Having greatest relation to embodiments of the invention described herein are Tong has described degenerate four wave-mixing and apparatus therein in U.S. Pat. Nos. 5,600,444 and 6,141,094 and Patent Application 2006263777. These describe apparati and methods that in their capacities are capable of analyzing small quantities of analytes down to a detection level of attomoles. They utilize different complements of analysis systems including HPLC and HCPE and a gas phase atomizer type spectroscopy. Furthermore, the dissertation “Protein Analysis at the Single Cell Level by Nonlinear Laser Wave-Mixing Spectroscopy for High Throughput Capillary Electrophoresis Applications” from Sadri's PhD dissertation N.C. State from 2008 relates similar apparati discussed in the Tong patents that reach the levels of detection of yoctomoles (10−24). The named articles, dissertations and patents are incorporated by reference in their entirety. These references give a background into the theories, adjustments and variations upon the technology that are explanatory. Similarly, supercritical fluid chromatography (SFC) has been explained and describe in many patents and journal articles. A review article gives a good example of the technology as used with chiral compounds “Enantioseparations in super- and subcritical fluid chromatography” Gerald Terfloth, J. Chromatogr. A 906 (2001) 301-307. This reference gives a modern view of how SFC is used with the different column technologies and instrumentation techniques. Some advantages of SFC are: higher efficiency, wider range of selectivity, longer column lifetime, lower solvent and waste disposal cost, using less toxic solvents and faster run time and overall more environmentally cleaner than other techniques.
As used in this specification and in the appended claims, the singular forms “a,” an” and “the” include plural references unless the content clearly dictates otherwise.
In describing the invention and embodiments, the following terms will be employed and are intended to be defined as indicated below. If any terms are not fully defined, then the normal usage as used in the art will fill any gaps in the understanding of the terminology.
Laser: is a device that creates a beam of light where all of the photons are in a coherent state—usually with the same frequency and phase. Among the other effects, this means that the light from a laser is often tightly focused and does not diverge much, resulting in the traditional laser beam. In free space, the beams inside and outside the cavity are usually Gaussian distributed and are highly collimated with very small divergence. The distance over which the laser beam remains collimated depends on the square of the beam diameter while divergence angle varies inversely with the beam diameter.
Collimating: is the process of making light rays parallel from a mixture of diverging light rays or beams, and therefore will spread slowly as it propagates. The word is related to “collinear” and implies light that does not disperse with distance (ideally), or that will disperse minimally (in reality). A perfectly collimated beam with no divergence cannot be created due to diffraction, but light can be approximately collimated by a number of processes, for instance by means of a collimator. A focusing lens with high focal point (1000 mm) is an example collimating lens.
Diagnostic flow technology: Is a solid state technology through a series of pumps or pump like mechanisms (such as electroosmotic flow, electrophoretic flow, capillary action, siphoning, pressure, imploding gas bubbles and the like) and apparati move analytes from a sample collection area to an analysis area which comprise of multiple detectors types such as photodiode arrays (PDA), ultraviolet-visible (UV-VIS) spectrometers, charge coupled device (CCD) (such as Fourier Transform Infrared (FT-IR)}, Nuclear Magnetic Resonance (NMR) detectors, Refractive Index spectrometers (RI), fluorescence detectors, radiation photomultipliers, and the like. Flow can be achieved through liquids, fluids, gas or other means pumped or other means driven through a series of channels and mediums (such as tubing or silica gels) to move analytes from one point to another. Examples would comprise but not limited to Liquid Chromatography (LC) (which would further comprises variations such as micellar, ion exchange and the like), Reverse Phase High Performance Liquid Chromatography (RP-HPLC), Gas Chromatography (GC), High Performance Capillary Electrophoresis (HPCE), Capillary Zone Electrophoresis (CZE), Supercritical Fluid Chromatography (SFC), Sub-critical Fluid Chromatography (SubFC), Inductively Coupled Plasma (ICP), and the like. Each technology is unique unto its own with positives and negatives propagating from each in achieving the needs of the user. For example, capillary electrophoresis has environmental positives in utilizing very little hazardous materials but has negative issues in what substances can be an analyzed and in what solvents are compatible.
Focal spot: an area or point onto which collimated light parallel to the axis of a lens is focused. This spot of light can be expanded and contracted in different shapes and geometries by some means such as a cylindrical lens.
Absorptive interaction: interaction of analytes in a flow cell chamber or multi channel chamber that creates a signal through the beam wave mixing when the two input beams form light induced gratings and an input beam is diffracted off this grating when analytes absorb the excitation light beam. The excited molecules in the form of interference patterns release their heat energy to surrounding solvent or matrix molecules, creating dynamic thermal gratings, and as a result, refractive index gratings. The incoming photons from the probe beam diffract off the gratings to generate the output signal beams.
Multichannel chamber: an enclosed space in which is configured to allow an absorptive interaction between multiple analytes and light beams. Multichannel flow cells and capillary arrays can be situated in a multichannel chamber.